Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16987 | 51184;51185;51186 | chr2:178611170;178611169;178611168 | chr2:179475897;179475896;179475895 |
| N2AB | 15346 | 46261;46262;46263 | chr2:178611170;178611169;178611168 | chr2:179475897;179475896;179475895 |
| N2A | 14419 | 43480;43481;43482 | chr2:178611170;178611169;178611168 | chr2:179475897;179475896;179475895 |
| N2B | 7922 | 23989;23990;23991 | chr2:178611170;178611169;178611168 | chr2:179475897;179475896;179475895 |
| Novex-1 | 8047 | 24364;24365;24366 | chr2:178611170;178611169;178611168 | chr2:179475897;179475896;179475895 |
| Novex-2 | 8114 | 24565;24566;24567 | chr2:178611170;178611169;178611168 | chr2:179475897;179475896;179475895 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs532794938  |
-0.648 | 0.627 | N | 0.586 | 0.175 | 0.257786959452 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 1.29316E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/R | rs532794938 |
-0.648 | 0.627 | N | 0.586 | 0.175 | 0.257786959452 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 1.44809E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | rs532794938 |
-0.648 | 0.627 | N | 0.586 | 0.175 | 0.257786959452 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| S/R | rs532794938 |
-0.648 | 0.627 | N | 0.586 | 0.175 | 0.257786959452 | gnomAD-4.0.0 | 8.68048E-06 | None | None | None | None | N | None | 1.7337E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.60195E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0857 | likely_benign | 0.0866 | benign | -0.767 | Destabilizing | 0.054 | N | 0.407 | neutral | None | None | None | None | N |
| S/C | 0.103 | likely_benign | 0.0985 | benign | -0.395 | Destabilizing | 0.928 | D | 0.58 | neutral | D | 0.576763132 | None | None | N |
| S/D | 0.4563 | ambiguous | 0.4957 | ambiguous | -0.365 | Destabilizing | 0.388 | N | 0.559 | neutral | None | None | None | None | N |
| S/E | 0.5055 | ambiguous | 0.5179 | ambiguous | -0.313 | Destabilizing | 0.388 | N | 0.559 | neutral | None | None | None | None | N |
| S/F | 0.1469 | likely_benign | 0.1581 | benign | -0.799 | Destabilizing | 0.69 | D | 0.599 | neutral | None | None | None | None | N |
| S/G | 0.1321 | likely_benign | 0.1341 | benign | -1.074 | Destabilizing | 0.324 | N | 0.557 | neutral | D | 0.57429439 | None | None | N |
| S/H | 0.2477 | likely_benign | 0.2536 | benign | -1.453 | Destabilizing | 0.981 | D | 0.582 | neutral | None | None | None | None | N |
| S/I | 0.1026 | likely_benign | 0.1086 | benign | -0.04 | Destabilizing | 0.076 | N | 0.583 | neutral | N | 0.504157679 | None | None | N |
| S/K | 0.4762 | ambiguous | 0.5002 | ambiguous | -0.616 | Destabilizing | 0.388 | N | 0.557 | neutral | None | None | None | None | N |
| S/L | 0.084 | likely_benign | 0.0863 | benign | -0.04 | Destabilizing | 0.116 | N | 0.56 | neutral | None | None | None | None | N |
| S/M | 0.1463 | likely_benign | 0.1548 | benign | 0.144 | Stabilizing | 0.69 | D | 0.595 | neutral | None | None | None | None | N |
| S/N | 0.1269 | likely_benign | 0.1398 | benign | -0.736 | Destabilizing | 0.324 | N | 0.571 | neutral | N | 0.51662281 | None | None | N |
| S/P | 0.9212 | likely_pathogenic | 0.9244 | pathogenic | -0.247 | Destabilizing | 0.818 | D | 0.581 | neutral | None | None | None | None | N |
| S/Q | 0.3906 | ambiguous | 0.4124 | ambiguous | -0.745 | Destabilizing | 0.818 | D | 0.564 | neutral | None | None | None | None | N |
| S/R | 0.4221 | ambiguous | 0.4334 | ambiguous | -0.616 | Destabilizing | 0.627 | D | 0.586 | neutral | N | 0.488303874 | None | None | N |
| S/T | 0.0593 | likely_benign | 0.0617 | benign | -0.668 | Destabilizing | None | N | 0.235 | neutral | N | 0.400282408 | None | None | N |
| S/V | 0.1272 | likely_benign | 0.1342 | benign | -0.247 | Destabilizing | 0.002 | N | 0.425 | neutral | None | None | None | None | N |
| S/W | 0.3237 | likely_benign | 0.3162 | benign | -0.851 | Destabilizing | 0.981 | D | 0.682 | prob.neutral | None | None | None | None | N |
| S/Y | 0.1789 | likely_benign | 0.1869 | benign | -0.55 | Destabilizing | 0.818 | D | 0.617 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.